According to the 2020 China Stroke Report, 50.9% of adults over the age of 18 without a history of hypertension in mainland China were in prehypertension, and the weighted prevalence of hypertension in adults aged 18 years and above was 27.5%, including 30.8% in men and 24.2% in women. The prevalence of hypertension in rural residents (29.4%) was higher than that in urban residents (25.7%). Only 41.0% of adults with hypertension were aware of their condition, 34.9% were taking antihypertensive drugs, and 11.0% had their blood pressure under control.
High blood pressure remains one of the important risk factors for stroke. There is a close causal relationship between blood pressure level and the occurrence and mortality of cardiovascular and cerebrovascular events. One meta-analysis found that a 20 mmHg increase in systolic blood pressure (SBP) or a 10 mmHg increase in diastolic blood pressure (DBP) was associated with a more than two-fold increase in stroke-related deaths, ischaemic heart disease, and other vascular causes between the ages of 40 and 69 years1. Another meta-analysis showed that antihypertensive therapy had the greatest benefit in stroke prevention, reducing the risk of stroke by approximately 36%2. It is of great clinical significance to pay attention to stroke blood pressure management. This newspaper specially invited Professor Li Gang to share his clinical experience in stroke blood pressure management.
Expert Profile
Professor Li Gang is the Affiliated East Hospital of Tongji University
Chief Physician, Professor, Doctoral Supervisor
He is currently the Deputy Secretary of the Party Committee and Vice President of the East Hospital Affiliated to Tongji University
Director of the Department of Neurology and Director of the Stroke Center
He is also the chairman of the Disaster Prevention Medicine Branch of the Chinese Preventive Medicine Association
Vice President of Neurologist Branch of Shanghai Medical Doctor Association
Group leader, Cerebrovascular Group, Neurology Branch, Shanghai Medical Association
Member of the Cerebrovascular Group of the Neurology Branch of the Chinese Medical Association
Member of the Standing Committee of the Interventional Neurology Committee of the Chinese Association of Research Hospitals
He is mainly engaged in clinical and basic research on pre-hospital emergency and cognitive dysfunction of cerebrovascular diseases
Sprouting from old trees: mean systolic blood pressure and blood pressure variability can be used as predictors
In recent years, significant progress has been made in guidelines and research on stroke blood pressure management, and new treatment strategies and methods have emerged. In 2023, 21-year follow-up results from the ASCOT study were published3, and amlodipine treatment-based patients had a significantly lower risk of stroke compared with atenolol-based therapy [HR 0.82 (95% CI 0.72-0.93), P=0.003], total cerebrovascular (CV) events [HR 0.93 (95% CI 0.88-0.98), P=0.008], and total coronary events [HR 0.92 (95% CI 0.86-0.99). ), P = 0.024], atrial fibrillation [HR 0.91 (95% CI 0.83-0.99), P = 0.030], and evidence for a difference in CV mortality was weak [HR 0.91 (95% CI 0.82-1.01), P = 0.073].
The study found that mean SBP was a predictor of a 19% increase in the risk of non-lethal/fatal stroke for every 10 mmHg increase in SBP (P<0.001). The absolute difference in mean systolic blood pressure between amlodipine + perindopril (136.3 mmHg) and atenolol + thiazide diuretics (138.0 mmHg) group was small but statistically significant (P<0.001).
Blood pressure variability (BPV), independent of mean SBP, was also a strong predictor of CV events (HR/5 mmHg 1.22 (95% CI 1.18-1.26), P<0.001), even in well-controlled participants. The BPV (10.8 mmHg) in the amlodipine + perindopril group was also significantly lower than that in the atenolol ± thiazide group (12.8 mmHg) (P<0.001). The long-term benefit of amlodipine + perindopril compared to atenolol-based therapy can be explained in part by its effect on SBP variability.
Blood pressure management in stroke: intensive antihypertensive therapy Reduced risk of stroke recurrence Follow an individualized approach
The Guidelines for Blood Pressure Management for the Prevention and Treatment of Stroke in China (2021 Edition) points out that blood pressure management is an important part of the primary prevention of stroke, and the blood pressure of high-risk groups should be < 130/80 mmHg. Meta-analyses have shown that intensive blood pressure lowering can significantly reduce the risk of stroke recurrence4 (Figure 1).
Figure 1: Intensive blood pressure lowering is associated with a smaller risk of stroke recurrence
The analysis also found that greater reductions in SBP and DBP were associated with a greater reduction in the risk of stroke recurrence, with a DBP reduction of more than 4 mmHg and a 46% reduction in the risk of stroke recurrence when SBP was reduced by more than 11 mmHg4.
ASCOT is a multicenter randomized trial with a 2×2 factorial design. Patients with hypertension in the UK were followed for all-cause mortality and cardiovascular mortality with a median follow-up of 15.7 years (IQR 9.7 to 16.4 years). At baseline, all patients included in the ASCOT antihypertensive arm (BPLA) were randomly assigned to receive either amlodipine-based or atenolol-based antihypertensive therapy. Among these patients, those with total cholesterol of 6.5 mmol/L or less and who had not received prior lipid-lowering therapy were further randomized to receive atorvastatin or placebo as part of the ASCOT lipid-lowering arm (LLA). The remaining patients were in the non-LLA group. The ASCOT-BPLA study confirmed that amlodipine combined with perindopril significantly reduced the risk of fatal and non-fatal stroke by 23% (P=0.0003)5. In the ASCOT-Legacy study with a median follow-up of 15.7 years, amlodipine in combination with perindopril also provided sustained cardiovascular benefits, reducing the risk of stroke death by 29% in the overall population6 (P=0.0305).
For intensive blood pressure lowering, it is necessary to treat it individually in clinical practice. A 2023 Korean multicenter, open-label, randomized controlled clinical study in the Journal of the American Medical Association (JAMA)7 found that in patients with acute ischemic stroke with successful intravascular thrombectomy (EVT) reperfusion, patients with large vessel occlusion were less likely to be functionally independent at 3 months after 24 hours of intensive blood pressure management compared with conventional blood pressure management. These results suggest that intensive blood pressure management should be avoided after successful EVT in acute ischemic stroke.
SPC drug combination punch Better adherence Better blood pressure lowering target
The 2018 European Society of Cardiology/European Society of Hypertension (ESC/ESH) guidelines have identified poor adherence to treatment as an important cause of poor blood pressure control. Approximately 43% to 66% of patients do not take their hypertension medication as prescribed, and 40% of patients discontinue the medication after one year, and simplifying the regimen improves adherence and blood pressure control. A systematic review and meta-analysis study showed that the use of SPC has significant advantages over monotherapy (FEC) in terms of medication adherence, drug use persistence, greater SBP reduction, and higher blood pressure compliance rates (Figure 2)8.
Figure 2: Comparison of medication adherence, medication persistence, and BP blood pressure reduction targets between the SPC and FEC groups
SPC has also been recommended by national guidelines. The 2018 European ESC/ESH guidelines recommend two-agent therapy for patients with initial hypertension9:
•For the initial treatment of hypertension in most people, a two-drug combination is preferred.
•Monolithic treatment strategy for hypertension, with SPC being the preferred treatment for most patients.
•Simplify the algorithm for pharmacotherapy, preferably with ACE inhibitors or ARBs in combination with CCBs and/or thiazide diuretics as the core treatment strategy for most patients, β receptor blockers for specific indications.
The 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the prevention and treatment of hypertension in the United States recommend 10: For adults with stage 2 hypertension (≥140/90 mmHg) and mean blood pressure above the target blood pressure of 20/10 mmHg, two different classes of first-line antihypertensive drugs can be initiated, and separate drugs can be used in combination with or fixed combinations (level I recommendation).
China's 2018 guidelines for the prevention and treatment of hypertension recommendation 11: For high-risk patients with blood pressure ≥ 160/100 mmHg, 20/10 mmHg higher than the target blood pressure, or hypertensive patients who fail to meet the target with monotherapy, combined antihypertensive therapy should be given, including free combination or single tablet combination preparation. For patients with blood pressure ≥ 140/90 mmHg, small doses of combined therapy can also be initiated, which can be freely combined or used in a single tablet combination preparation. Method of combination medication: when the two drugs are combined, the antihypertensive mechanism should be complementary, and at the same time have an additive antihypertensive effect, and can cancel each other or reduce adverse reactions. For example, the addition of a low-dose thiazide diuretic to an ACE inhibitor or ARB can lower blood pressure by as much as or more than the dose of an ACE inhibitor or ARB. Similarly, the addition of dihydropyridine CCBs has a similar effect.
The half-life of SPC composed of amlodipine and perindopril is > 30 hours, and it can reduce blood pressure for a long time for 24 hours, which shows unique advantages in stroke blood pressure management as a commonly used antihypertensive drug. For SPC of indapamide and perindopril, there is evidence-based evidence for perindopril in crossing the blood-brain barrier, capillary remodeling, and improving endothelial function. The PROGRESS study has confirmed that perindopril has good efficacy in reducing blood pressure on the basis of high-quality blood pressure, stable blood pressure lowering, and reducing blood pressure fluctuations, etc., in terms of brain attention and recovery of cerebrovascular self-regulation ability.
Proper blood pressure management is of great significance for improving the prognosis of stroke patients, promoting functional recovery and improving quality of life. Future research on stroke blood pressure management needs to focus on the development of new drugs and the optimization of treatment strategies, while also facing the challenges of patient diversity and treatment complexity. In light of China's national conditions, it is necessary to develop blood pressure management strategies suitable for Chinese patients to improve the popularity and effectiveness of treatment.
Conclusion
Hypertension is still the primary risk factor for stroke, and it is a top priority to effectively control blood pressure, improve the treatment effect and quality of life of stroke patients, and achieve the goal of Healthy China 2030 as soon as possible. Based on the antihypertensive concept of strengthening blood pressure lowering and achieving the goal as soon as possible, SPC has shown obvious advantages in stroke blood pressure management and has been recommended by national guidelines. By achieving lower blood pressure reduction targets, this SPC helps to reduce the rate of stroke recurrence and improve long-term patient outcomes. However, in practice, it is still necessary to adjust the treatment plan individually according to the specific situation of the patient and the doctor's recommendation.
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